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. 2022 Apr 27;8(1):44.
doi: 10.1038/s41537-022-00249-5.

Role of advanced glycation end products in the longitudinal association between muscular strength and psychotic symptoms among adolescents

Kazuhiro Suzuki #  1   2   3   4 , Syudo Yamasaki #  5 , Mitsuhiro Miyashita #  1   3 , Shuntaro Ando  6 , Kazuya Toriumi  1 , Akane Yoshikawa  1   3 , Miharu Nakanishi  5 , Yuko Morimoto  5 , Sho Kanata  6 , Shinya Fujikawa  6 , Kaori Endo  5 , Shinsuke Koike  7 , Satoshi Usami  8 , Masanari Itokawa  1   3 , Shinsuke Washizuka  2   4 , Mariko Hiraiwa-Hasegawa  9 , Herbert Y Meltzer  10 , Kiyoto Kasai  6   11 , Atsushi Nishida  12 , Makoto Arai  1
Affiliations

Role of advanced glycation end products in the longitudinal association between muscular strength and psychotic symptoms among adolescents

Kazuhiro Suzuki et al. Schizophrenia (Heidelb). .

Abstract

Muscular strength, assessed by handgrip, is a risk indicator for psychiatric disorders, including psychosis. However, the biological mechanisms underlying this association remain unclear. Since advanced glycation end products (AGEs) play a key role in skeletal muscle underdevelopment and psychosis, we examined the role of AGEs in the longitudinal association between muscular strength and psychotic symptoms among adolescents. We first evaluated the direction of the relationship between handgrip strength and urine levels of pentosidine, a representative AGEs in a population-based birth cohort of 1,542 adolescents at ages 12 and 14. Then, we examined the role of AGEs in the longitudinal association between handgrip strength and thought problems (TP), as a psychotic symptom indicator, in a subsample of 256 adolescents at ages 13 and 14. An autoregressive cross-lagged model revealed that handgrip strength at age 12 negatively predicted pentosidine levels at age 14 (β = -0.20, p < 0.001), whereas pentosidine levels at age 12 did not predict handgrip strength at age 14 (β = 0.04, p = 0.062). Moreover, pentosidine levels had a significant indirect effect on the relationship between handgrip strength and TP (standard indirect effect = -0.051, p = 0.012), which remained significant after adjusting for gender and preceded TP and pentosidine levels. Thus, adolescents with low muscular strength are at a high risk of developing psychotic symptoms, which could be mediated by AGEs. Future studies need to investigate whether interventions focused on muscular strength prevent the accumulation of AGEs and thereby prevent the development of psychosis.

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Conflict of interest statement

K.S., S.Y., M.M., S.A., K.K., A.N., and M.A. received grant support from the Japan Society for the Promotion of Science during the conduct of the study. M.M., M.I., and M.A. have a patent (PCT/JP2008/063803) with royalties paid to Kowa Co. Ltd., outside the submitted work. KK received grant support from MSD, Astellas, Sumitomo Dainippon Pharma, Eisai, Lily, Takeda, and Mitsubishi Tanabe Pharma. K.K. reports personal fees from Daiichi Sankyo, Otsuka, Meiji Seika Pharma, MSD, Yoshitomi, Astellas, Mochida, Sumitomo Dainippon, Eisai, and Fuji-Film RI Pharma outside the submitted work. M.A. received grant support from the Uehara Memorial Foundation, the Sumitomo Foundation, and the SENSHIN Medical Research Foundation. H.Y.M. received grant support from ACADIA, Allergan, Eli Lilly, Janssen, Quincy Pharmaceutical, Sumitomo Dainippon, and Sunovion. H.Y.M. is a stockholder of ACADIA. The remaining authors declare no competing interests.

Figures

Fig. 1
Fig. 1. Cross-lagged panel model showing the direction of association between handgrip strength and pentosidine levels.
Note: Solid black line, path coefficient is statistically significant (p < 0.05); dotted line, path coefficient is not significant (p ≥ 0.05).
Fig. 2
Fig. 2. Path diagram describing the indirect effect between handgrip strength and thought problems via pentosidine.
Note: solid black line, path coefficient is statistically significant (p < 0.05); dotted line, path coefficient is not significant (p ≥ 0.05). CFI: comparative fit index, RMSEA: root mean square error of approximation.
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References

    1. Arieti, S. Heredity and constitution in schizophrenia in Interpretation of Schizophrenia (London: Jason Aronson Inc., 1974) 441–451.
    1. Kretschmer, E. Physique and Character: an Investigation of the Nature of Constitution and of the Theory of Temperament; with 31 Plates (London: Kegan Paul, Trench, Trubner, 1926).
    1. Meltzer HY, Moline R. Muscle abnormalities in acute psychoses. Arch. Gen. Psychiatry. 1970;23:481–491. - PubMed
    1. Meltzer HY. Neuromuscular dysfunction in schizophrenia. Schizophr. Bull. 1976;2:106–135. - PubMed
    1. Fish B. Neurobiologic antecedents of schizophrenia in children. Evidence for an inherited, congenital neurointegrative defect. Arch. Gen. Psychiatry. 1977;34:1297–1313. - PubMed